We have found Nisei (second-generation Japanese American) men living in King County, Washington, to have high prevalence rates of impaired glucose tolerance (IGT) and diabetes (noninsulin-dependent). These rates are much higher than observed in comparably aged U.S. Caucasians or native Japanese in Japan. Nisei men also have a high prevalence of ischemic heart disease associated with IGT and diabetes. Our data suggest that Japanese may have an inherent tendency to develop abnormal glucose tolerance and atherosclerotic cardiovascular disease, and that these conditions become frequent when certain "environmental" variables intervene. Some of these variables appear to be diet, health habits, psychosocial stress, and cultural factors. We hypothesize that in conjunction with heredity and other biologic factors, including aging, these variables influence the development of a distinctive pattern of adiposity (abdominal), hyperinsulinemia, and glucose tolerance. In turn, hyperinsulinemia and glucose intolerance appear to lead to atherosclerosis, while hyperglycemia is a risk for development of microangiopathy and neuropathy. To examine this hypothesis from an epidemiologic perspective, we propose in the next 5-year project period to expand our current 3-year cross-sectional project in Nisei men to include also Nisei women and Sansei (third generation Japanese American) men and women. Our objective is to clarify conditions responsible for the development of IGT, diabetes, and associated complications; their prevalence and incidence rates and the subsequent course of those with IGT. Some of the factors to be examined are age, adiposity, pattern of body fat, medications, blood pressure, glycemia, plasma lipids, hormone levels, diet, family history, life style, sociocultural characteristics, and social stress. To accomplish these goals, we will use a longitudinal approach re-examining the Nisei men and doing initial and follow-up studies in Nisei women. In Sansei, we intend to gather baseline data on possible precursors to glucose intolerance and cardiovascular disease. Taking into consideration the availability of racially homogenous and chronologically discrete age groups (generations) within the Japanese American population, the long exposure to Western life style, the current middle-class socioeconomic status, the stability of the population, the high prevalence of glucose intolerance, we are in a unique position to examine, in a population setting that includes many of the environmental conditions relevant to the larger U.S. population, the above hypothesized relationships.